BI03 The presence of VEXAS-related UBA1 mutation in a patient with myelodysplastic syndrome

A 56-year-old female patient with a background of myelo­dysplastic syndrome (MDS) was admitted with a febrile illness and a solitary, bullous skin lesion on her right inner thigh. This lesion started as a scaly patch 1 week prior to admission before developing into a large tense bulla with associated lymphadenopathy in the groin. The patient had a background of MDS, which was being treated with donor lymphocyte infusions, having relapsed from a previous allogeneic bone marrow transplant. Initial treatment was with intravenous antibiotics. While ultrasound did not reveal any clear underlying abscess, surgical debridement was performed due to the patient’s deteriorating clinical state and concerns about an infective focus within the wound. Histological analysis showed a neutrophilic infiltrate, raising suspicion of pyoderma gangrenosum or other neutrophilic dermatoses. A UBA1 mutation of uncertain significance was detected in the perivascular histiocytes, raising the possibility of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Following debridement and exclusion of an infective aetiology, the wound was managed with vacuum-assisted wound closure and a slowly weaning course of 40 mg oral prednisolone over 4 months. The patient subsequently underwent a second allogeneic bone marrow transplant, complicated by sepsis and requiring admission to critical care. During this hospitalization, she developed haemorrhagic lesions that were also considered to be due to an inflammatory process driven by her MDS. These were resolved following initiation of cyclophosphamide immunosuppression after her transplant. The cutaneous manifestations of MDS encompass neutrophilic dermatoses, cutaneous vasculitis and granulomatous skin lesions. Recognition of these manifestations has therapeutic and prognostic importance, as they can precede a diagnosis of MDS and be an indicator of poor prognosis. Differentiating classic MDS from VEXAS syndrome is critical, as the latter lacks additional molecular abnormalities and exhibits less cytological heterogeneity. However, a complex interplay exists between MDS and systemic autoimmune/autoinflammatory diseases (AID), with an undefined pathophysiological mechanism. In this case, we describe the development of known AID associated with underlying MDS in the presence of a VEXAS-related UBA1 mutation, which is responding favourably to stem cell transplant and immunosuppression. The patient is currently in recovery without further skin manifestations.